IL-18 promotes NK cell and Th1 cell activity and may bridge innate and adaptive immune responses. Myelin oligodendrocytes glycoprotein (MOG) is a myelin component of the CNS and is a candidate autoantigen in multiple sclerosis. In the present study we show that IL-18-deficient (IL-18(-/-)) mice are defective in mounting autoreactive Th1 and autoantibody responses and are resistant to MOG35-55 peptide-induced autoimmune encephalomyelitis. IL-18 administration enhances the disease severity in wild-type mice and restores the ability to generate Th1 response in the IL-18(-/-) mice. This restoration was abrogated in NK cell-depleted mice, indicating that the action of IL-18 in promoting the generation of MOG-specific Th cells was dependent on NK cells. Furthermore, transfer of NK cells from recombinase-activating gene 1(-/-) mice, but not from recombinase-activating gene 1/IFN-γ(-/-) mice, rescued the defective Th1 responses in IL-18(-/-) mice and rendered IL-18(-/-) mice susceptible to the induction of autoimmune encephalomyelitis. Thus, IL-18 can direct autoreactive T cells and promote autodestruction in the CNS at least in part via induction of IFN-γ by NK cells.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Immunology|
|State||Published - Sep 15 2000|
ASJC Scopus subject areas
- Immunology and Allergy